Pracinostat

Acute Myeloid Leukemia

Unfit for intensive chemotherapy

Vidaza® (azacitidine)

Pre-Clinical

Clinical Proof-Of-Concept

Pivotal

INDICATION / COMBINATION

Myelodysplastic Syndrome

High & very high risk

Vidaza® (azacitidine)

Pre-Clinical

Clinical Proof-Of-Concept

Pivotal

OVERVIEW

Pracinostat is an oral histone deacetylase ("HDAC") inhibitor that is in a pivotal Phase 3 study in combination with azacitidine for the treatment of adults with newly diagnosed acute myeloid leukemia ("AML") who are unfit for intensive chemotherapy. It is also being evaluated in a Phase 2 study in patients with high or very high-risk myelodysplastic syndrome ("MDS"). The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy.

In August 2016, Helsinn Group and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. The agreement provides that Helsinn is primarily responsible for development and commercialization costs for pracinostat in AML and other indications, including MDS. Pracinostat is an investigational agent and is not approved for commercial use in the U.S. and any country worldwide.

MECHANISM OF ACTION

HDAC inhibitors belong to a larger set of proteins collectively known as epigenetic regulators that can alter gene expression by chemically modifying DNA or its associated chromosomal proteins. Abnormal activity of these regulators is believed to play an important role in cancer and other diseases.

ABOUT AML

Acute myeloid leukemia (AML) is the most common type of acute leukemia. It is a fast-growing form of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells or platelets. AML has eight different subtypes, which are based on the cell from which the leukemia developed.

ABOUT MDS

Myelodysplastic Syndrome is a type of blood cancer in which the bone marrow does not make enough healthy blood. MDS is normally a disease of the elderly and sometimes may progress into AML, which is a more rapidly growing cancer.

CLINICAL PROGRAM

The ongoing pivotal Phase 3 registration study is being conducted by Helsinn and was initiated in June of 2017. It is a randomized, double-blind, placebo-controlled study that will enroll approximately 500 adults worldwide with newly diagnosed AML who are unfit to receive intensive chemotherapy. The primary endpoint of the study is overall survival. This registration study follows a Phase 2 study of pracinostat plus azacitidine in elderly patients with newly diagnosed AML who are not candidates for induction chemotherapy that demonstrated a median overall survival of 19.1 months and a complete remission (“CR”) rate of 42% (21 of 50 patients). These data compare favorably to an international Phase 3 study of azacitidine (AZA-001; Dombret et al. Blood. 2015 May 18), which showed a median overall survival of 10.4 months with azacitidine alone and a CR rate of 19.5% in a similar patient population. The combination of pracinostat and azacitidine was generally well tolerated, with no unexpected toxicities.

Additionally, pracinostat is being investigated in an open-label, Phase 2 dose optimization study evaluating approximately 60 patients with high and very high-risk MDS who are previously untreated with hypomethylating agents. The Phase 2 open-label study is evaluating a 45mg dose of pracinostat in combination with the standard dose of azacitidine. A successful pre-planned interim analysis in this Phase 2 study demonstrated a 10% discontinuation rate among the first 20 evaluable patients treated, beating the predefined threshold in the first 3 treatment cycles. The 10% rate is consistent with the established discontinuation rate for azacitidine given as a monotherapy.

The study is designed to improve tolerability and retain patients in the study longer than in an earlier Phase 2 study evaluating a 60 mg dose. A prolonged treatment may result in a systemic exposure to pracinostat sufficient to achieve the desired treatment effect; data from the earlier Phase 2 study suggested that insufficient exposure to treatment may have limited overall efficacy of the combination.

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